Du Pengfei, Xia Tianqi, Li Xuxin, Giri Bikash R, Fang Chuantao, Li Shun, Yan Shi, Cheng Guofeng
Shanghai Tenth People's Hospital, Institute for Infectious Diseases and Vaccine Development, School of Medicine, Tongji University, Shanghai, China.
Shanghai Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Key Laboratory of Animal Parasitology of Ministry of Agriculture and Rural Affairs, Shanghai, China.
Commun Biol. 2024 Dec 31;7(1):1717. doi: 10.1038/s42003-024-07402-z.
Adult Schistosoma produces a large number of eggs that play essential roles in host pathology and disease dissemination. Consequently, understanding the mechanisms of sexual maturation and egg production may open a new avenue for controlling schistosomiasis. Here, we describe that Bantam miRNA and miR-1989 regulate Wnt signaling pathway by targeting Frizzled-5/7/9, which is involved in ovarian development and oviposition. Additionally, Frizzled-7 could cooperate with SjRho to maintain normal ovarian development and egg productions and SjRho may interact with Hsp60 to potentially support Frizzled-7 trafficking and signaling. Further in vivo inhibition of SjRho in mice model infected with Schistosoma results in a remarkable decrease in worm burden and egg productions. Our findings not only broaden the functions of Bantam miRNA and miR-1989 as well as Wnt signaling pathway, but also imply that interruption of Bantam/miR-1989-Frizzled-5/7/9-SjRho axis may serve as effective targets against schistosomiasis.
成年血吸虫会产生大量虫卵,这些虫卵在宿主病理和疾病传播中起着至关重要的作用。因此,了解性成熟和产卵机制可能为控制血吸虫病开辟一条新途径。在此,我们描述了Bantam miRNA和miR-1989通过靶向卷曲蛋白-5/7/9来调节Wnt信号通路,卷曲蛋白-5/7/9参与卵巢发育和产卵过程。此外,卷曲蛋白-7可与日本血吸虫Rho蛋白(SjRho)协同作用,以维持正常的卵巢发育和产卵,并且SjRho可能与热休克蛋白60(Hsp60)相互作用,从而潜在地支持卷曲蛋白-7的转运和信号传导。在感染血吸虫的小鼠模型中进一步对SjRho进行体内抑制,会导致虫体负荷和产卵量显著下降。我们的研究结果不仅拓宽了Bantam miRNA和miR-1989以及Wnt信号通路的功能,还表明阻断Bantam/miR-1989-卷曲蛋白-5/7/9-SjRho轴可能成为对抗血吸虫病的有效靶点。